Take into Account Variations of Transferrin Saturation

The statement on transferrin saturation (TSAT): “Iron deficiency is present if the TSAT is less than 20%, …” (1) is not correct. Only 0.07% of the total body iron (approximately 0.0035 g of 5 g) is bound to transferrin in the blood plasma, such that TSAT <20% indicates at most an iron deficiency in the blood plasma compartment and cannot be equated with a reduction in total body iron stores. In addition, the authors themselves point out the high variation of TSAT over the course of a day in the excellent part of their work in the “Iron overload” section, and they have rightly not included TSAT in the diagnostic algorithm (1). Although TSAT has a predictive value for iron supplementation in severe chronic heart failure, its predictive power is comparable to tossing a coin for oncological patients (2). For example, 30% of tumor patients with an adequate iron supply have TSAT <20%; conversely, 25% of them with an absolute iron deficiency have TSAT >20% (3). Unfortunately, these findings have so far only been implemented into the guidelines on tumor and chemotherapy-induced anemia from the National Comprehensive Cancer Network (NCCN), in which the previously used but scientifically unproven lower limit for TSAT of < 20% was changed (in version 2.2019) to define a functional iron deficiency at TSAT <50% with ferritin 30–500 mg/L.

Currently, analysis of the iron supply for erythropoiesis is based on measurements of the soluble transferrin receptor and the corpuscular hemoglobin of reticulocytes (CHR). CHR is automatically determined by modern blood count analyzers, and a value of <28 pg indicates that too little iron has been incorporated into the erythrocytes over the past 1 to 2 days. At the moment, CHR is considered the earliest indicator of both an iron-restricted erythropoiesis and a successful iron substitution (4).